Search

For a long time, ABO incompatible living donor kidney transplantation has been considered contraindicated, due to the presence of isohemagglutinins, natural antibodies reacting with non-self ABO antigens. However, as the demand for kidney transplantation is constantly growing, methods to expand the donor pool have become increasingly important. Thus, in the last decades, specific desensitization strategies for ABOi transplantation have been developed. Nowadays, these regimens consist of transient removal of preformed anti-A or anti-B antibodies by using plasmapheresis or immunoadsorption and B-cell immunity modulation by CD20+ cells depletion with rituximab, in association with maintenance immunosuppression including corticosteroids, tacrolimus and mycophenolate mofetil. The outcome in ABOi kidney transplantation have markedly improved over the years. In fact, although randomized trials are still lacking, recent meta analysis has revealed that there is no difference in terms of graft and patient's survival between ABOi and ABO compatible kidney transplant, even in the long term. However, many concerns still exist, because ABOi kidney transplantation is associated with an increased risk of bleeding and infectious complications, partly related to the effects of extracorporeal treatments and the strong immunosuppression. Thus, a continuous improvement in desensitization strategies, with the aim of minimize the immunosuppressive burden, on the basis of immune pathogenesis, antibodies titers and/or ABO blood group, is warranted. In this review, we discuss the main immune mechanisms involved in ABOi kidney transplantation, the pathogenesis of tolerance and the desensitization regimens, including immunoadsorption and plasmapheresis and the immunosuppressive protocol. Finally, we provide an overview on outcome and future perspectives in ABOi kidney transplant.

Background The acute and long-term effects of severe acute respiratory syndrome coronavirus 2 infection in individuals with GN are still unclear. To address this relevant issue, we created the International Registry of COVID-19 infection in GN.Methods We collected serial information on kidney-related and -unrelated outcomes from 125 GN patients (63 hospitalized and 62 outpatients) and 83 non-GN hospitalized patients with coronavirus disease 2019 (COVID-19) and a median follow-up period of 6.4 (interquartile range 2.3–9.6) months after diagnosis. We used logistic regression for the analyses of clinical outcomes and linear mixed models for the longitudinal analyses of eGFR. All multiple regression models were adjusted for age, sex, ethnicity, and renin-angiotensin-aldosterone system inhibitor use.Results After adjustment for pre-COVID-19 eGFR and other confounders, mortality and AKI did not differ between GN patients and controls (adjusted odds ratio for AKI=1.28; 95% confidence interval [CI], 0.46 to 3.60; P=0.64). The main predictor of AKI was pre-COVID-19 eGFR (adjusted odds ratio per 1 SD unit decrease in eGFR=3.04; 95% CI, 1.76 to 5.28; PConclusions Pre-COVID-19 eGFR is the main risk factor for AKI regardless of GN diagnosis. However, GN patients are at higher risk of impaired eGFR recovery after COVID-19-associated AKI. These patients (especially those with high baseline proteinuria or a diagnosis of focal segmental glomerulosclerosis or minimal change disease) should be closely monitored not only during the acute phases of COVID-19 but also after its resolution.

Background Diabetic donors are recognized as a reliable source of organs, although the discard rate of kidneys is still high. Few data are available on the histological evolution of these organs especially on kidneys transplanted into non-diabetic patients who remain euglycemic. Methods We describe the histological evolution of ten kidney biopsies performed on non-diabetic recipients of diabetic donors. Results Mean donor age was 69 ± 7 years, 60% were males. Two donors were treated with insulin, eight with oral antidiabetic drugs. Mean recipient age was 59.9 ± 7 years, 70% were males. The pre-existing diabetic lesions identified in the pre-implantation biopsies, encompassed all histological classes, and were associated with mild IF/TA and vascular damages. The median follow-up was 59.5 [IQR 32.5–99.0] months; at follow-up, 40% of cases did not change histologic classification, two patients with class IIb downgraded to IIa or I and one with class III downgraded to IIb. Conversely, three cases showed a worsening, from class 0 to I, I to IIb or from IIa to IIb. We also observed a moderate evolution of IF/TA and vascular damages. At follow-up visit, estimated GFR was stable (50.7 mL/min vs. 54.8 at baseline) and proteinuria was mild (51.1 ± 78.6 mg/day). Conclusions Kidneys from diabetic donors show variable evolution of the histologic features of diabetic nephropathy after transplant. This variability may be associated to recipients characteristics such as euglycemic milieu, in case of improvement, or obesity and hypertension, in case of worsening of histologic lesions.

The effects of SARS-CoV-2 infection on individuals with immune-mediated glomerulonephritis, who are often undergoing immunosuppressive treatments, are unknown. Therefore, we created the International Registry of COVID infection in glomerulonephritis (IRoc-GN) and identified 40 patients with glomerulonephritis and COVID-19 followed in centers in North America and Europe. Detailed information on glomerulonephritis diagnosis, kidney parameters, and baseline immunosuppression prior to infection were recorded, as well as clinical presentation, laboratory values, treatment, complications, and outcomes of COVID-19. This cohort was compared to 80 COVID-positive control cases from the general population without glomerulonephritis matched for the time of infection. The majority (70%) of the patients with glomerulonephritis and all the controls were hospitalized. Patients with glomerulonephritis had significantly higher mortality (15% vs. 5%, respectively) and acute kidney injury (39% vs. 14%) than controls, while the need for kidney replacement therapy was not statistically different between the two groups. Receiving immunosuppression or renin-angiotensin-aldosterone system inhibitors at presentation did not increase the risk of death or acute kidney injury in the glomerulonephritis cohort. In the cohort with glomerulonephritis, lower serum albumin at presentation and shorter duration of glomerular disease were associated with greater risk of acute kidney injury and need for kidney replacement therapy. No differences in outcomes occurred between patients with primary glomerulonephritis versus glomerulonephritis associated with a systemic autoimmune disease (lupus or vasculitis). Thus, due to the higher mortality and risk of acute kidney injury than in the general population without glomerulonephritis, patients with glomerulonephritis and COVID-19 should be carefully monitored, especially when they present with low serum albumin levels., Graphical abstract

Chronic kidney disease (CKD) is a complex and multifactorial disease, and one of the most prevalent worldwide. Chronic kidney disease–mineral bone disorders (CKD–MBD) with biochemical and hormonal alterations are part of the complications associated with the progression of CKD. Pathophysiology of CKD–MBD focused on abnormalities in serum levels of several biomarkers (such as FGF-23, klotho, phosphate, calcium, vitamin D, and PTH) which are discussed in this review. We therefore examine the prognostic association between CKD–MBD and the increased risk for cardiovascular events, mortality, and CKD progression to end-stage kidney disease (ESKD). Lastly, we present specific treatments acting on CKD to prevent and treat the complications associated with secondary hyperparathyroidism (SHPT): control of hyperphosphatemia (with dietary restriction, intestinal phosphate binders, and adequate dialysis), the use of calcimimetic agents, vitamin D, and analogues, and the use of bisphosphonates or denosumab in patients with osteoporosis.

Background and objectives: In patients with kidney failure due to IgA nephropathy, IgA deposits can recur in a subsequent kidney transplant. The incidence, effect, and risk factors of IgA nephropathy recurrence is unclear, because most studies have been single center and sample sizes are relatively small.Design, setting, participants, & measurements: We performed a multicenter, international, retrospective study to determine the incidence, risk factors, and treatment response of recurrent IgA nephropathy after kidney transplantation. Data were collected from all consecutive patients with biopsy-proven IgA nephropathy transplanted between 2005 and 2015, across 16 “The Post-Transplant Glomerular Disease” study centers in Europe, North America, and South America.Results: Out of 504 transplant recipients with IgA nephropathy, recurrent IgA deposits were identified by kidney biopsy in 82 patients; cumulative incidence of recurrence was 23% at 15 years (95% confidence interval, 14 to 34). Multivariable Cox regression revealed a higher risk for recurrence of IgA deposits in patients with a pre-emptive kidney transplant (hazard ratio, 3.45; 95% confidence interval, 1.31 to 9.17) and in patients with preformed donorspecific antibodies (hazardratio, 2.59; 95%confidence interval, 1.09 to 6.19).Afterkidneytransplantation,development of de novo donor-specific antibodies was associated with subsequent higher risk of recurrence of IgA nephropathy (hazard ratio, 6.65; 95% confidence interval, 3.33 to 13.27). Immunosuppressive regimen was not associated with recurrent IgA nephropathy in multivariable analysis, including steroid use. Graft loss was higher in patients with recurrence of IgA nephropathy compared with patients without (hazard ratio, 3.69; 95% confidence interval, 2.04 to 6.66), resulting in 32% (95% confidence interval, 50 to 82) graft loss at 8 years after diagnosis of recurrence.Conclusions: In our international cohort, cumulative risk of IgA nephropathy recurrence increased after transplant and was associated with a 3.7-fold greater risk of graft loss.

Although most patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) experience respiratory manifestations, multi-organ dysfunction is frequent. Almost 20% of hospitalized patients with SARS-CoV-2 infection develop acute kidney injury (AKI). The pathophysiology of AKI is a result of both the direct and indirect effects of SARS-CoV-2 infection, including systemic inflammatory responses, the activation of the renin-angiotensin-aldosterone system (RAAS), and endothelial and coagulative dysfunction. Underlying SARS-CoV-2 infection-associated AKI, an immunological hyper-response with an unbalanced innate and adaptative response defined as a “cytokine storm” has emerged. Numerous agents have been tested in an effort to mitigate the cytokine storm, and a range of extracorporeal cytokine removal techniques have been proposed as potential therapeutic options. In the present review, we summarize the main pathogenetic mechanisms underlying COVID-19-related AKI in order to provide an appropriate individual therapeutic strategy to improve clinical outcomes and limit the progression of early disease.

Background and Aims Several chronic medical conditions appear to increase the risk of severe COVID-19. Chronic kidney disease (CKD) patients have a high risk of symptomatic infection and severe respiratory symptoms because of chronic inflammation, uremic toxins accumulation, endothelial dysfunction and an impaired immune response. Even though the presence of one or more comorbidities increases the risk of mortality, information of the outcome of COVID-19 in CKD patients is not yet available. The aim of the study is to present the incidence and outcome of COVID-19 in patients referring to our Nephrology Unit considering CKD patients, dialysis patients and kidney transplant recipients. MO520 Table 1. Demographic, clinical and radiological features. Variables Total (n=52) Survivors (n=39) Nonsurvivors(n=13) Age, yr 67.2± 13.8 65± 14 72± 12 Woman 21 (39%) 17 (44.7%) 5 (13%) Comorbidity CV disease 41 (78.8%) 30 (79%) 11(84.6%) DM 22 (42%) 14 (36.8%) 8 (61.5%) Cancer 18 (31%) 12 (31.6%) 6(46.1%) BMI>30 7 (3%) 4(10.5%) 2(15.4%) Dialysis 31(59.5%) 24 (63.1) 6 (46%) Kidney transplantation 16 (30.7%) 11 (29%) 2 (15%) CKD IV-V stage 4 (7%) 2 (5.2%) 1 (7.7%) Onset of Symptoms fever 29 (79%) 22(58%) 7 (13%) cough 3(6%) 2 (5.2%) 1 (7.7%) dyspnea 8 (15.4%) 4 (10.5%) 4 (30.8%) Symptomless 8 (15.4%) 6 (15.8%) 2 (15.4%) Admission HRCT Bilateral peripheral ground-gass opacity 39(81.2%) 31 (79.5%) 8(88.8%) Unilateral opacity 6 (12.5%) 5(12.8%) 1 (11.1) No opacity 3 (6.2%) 3 (7.7%) 0 PaO2/FiO2 ratio 330 ± 102. 376 ±93 286 ±86 Method This study is prospective single centre carried out considering patients referring to the Nephrology Unit of St. Orsola University Hospital in Bologna with COVID 19 diagnosis from 15THMarch to 30THMay 2020. Results Our cohort included 52 patients admitted to our Nephrology Unit because of Sars Cov2 infection confirmed by positive reverse transcriptase polymerase chain reaction on nasopharyngeal swab. The mean age was 67.2 ± 13.8 years (range, 33-88 years). Demographic, clinical and radiological features in Table 1. Forty-eight patients (92.3%) underwent chest TC. The main findings were: several bilateral interstitial pneumonia (39 patients, 81.2%), monolateral peripheral ground-glass opacities (6 patients, 12.5%), no signs of pneumonia (3 patients, 6.2 %). Clinical course is highly variable: 18 patients (34.6 %) were asymptomatic, 23 patients (44 %) had a mild course requiring low flux oxygen therapy and 11 patients (21%) presented severe pneumonia and respiratory distress that requires ventilatory support in intensive care unit. Forty patients (70%) had hydroxychloroquine-azithromycin dual therapy, 3 patients (6%) had antiviral therapy in addiction. Sixteen patients (31%) with P/F

Purpose: Anastomotic pseudoaneurysms of transplanted kidneys are a very rare complication encountered in less than 1% of cases. They may be devastating, leading to functional impairment, kidney transplantectomy, or death. Treatment has not been standardized, with open surgical repair considered the safest procedure even if it is often complicated by bleeding and graft loss. The purpose of this case report is to describe an endovascular treatment of this condition, consisting of the combination of coil embolization and arterial stenting. Case report: A 61-year-old woman developed an anastomotic pseudoaneurysm 2 months after kidney transplantation, causing acute kidney injury related to ab-extrinsic stenosis of the transplant renal artery (TRA) and external iliac artery. The pseudoaneurysm was successfully treated by coil embolization, and the arterial patency was restored by the stenting of TRA and external iliac artery. The patient completely recovered kidney function, and after a 6-month-follow-up, creatinine values were stable with normal renal perfusion. Conclusion: Endovascular repair through coil embolization and TRA stenting can be a safe and effective option to treat anastomotic pseudoaneurysm in kidney transplant.

Diabetes is the leading cause of kidney failure and specifically, diabetic kidney disease (DKD) occurs in up to 30% of all diabetic patients. Kidney disease attributed to diabetes is a major contributor to the global burden of the disease in terms of clinical and socio-economic impact, not only because of the risk of progression to End-Stage Kidney Disease (ESKD), but also because of the associated increase in cardiovascular (CV) risk. Despite the introduction of novel treatments that allow us to reduce the risk of future outcomes, a striking residual cardiorenal risk has been reported. This risk is explained by both the heterogeneity of DKD and the individual variability in response to nephroprotective treatments. Strategies that have been proposed to improve DKD patient care are to develop novel biomarkers that classify with greater accuracy patients with respect to their future risk (prognostic) and biomarkers that are able to predict the response to nephroprotective treatment (predictive). In this review, we summarize the principal prognostic biomarkers of type 1 and type 2 diabetes and the novel markers that help clinicians to individualize treatments and the basis of the characteristics that predict an optimal response.

Multiple myeloma (MM) is the most common malignancy associated with end-stage renal disease; the presence of renal involvement reduces the median survival of patients with MM. Recently the term “monoclonal gammopathy of renal significance” (MGRS) has been defined that describes all B cell or plasma cell proliferative disorders that produce a monoclonal immunoglobulin associated with progressive kidney injury. The excessive amount of clonal light chains is completely filtered and adsorbed till the maximum capacity of proximal tubule that could be saturated, so the excess of FLC presents in the urine as Bence Jones proteinuria. The different biochemical characteristics of FLC determine a different histological involvement, which imply the variable clinical presentation ranging from severe acute kidney injury to chronic renal failure with different grade of proteinuria. Actual therapies are directed to prompt FLC removal from circulation by apheresis and control of their production by proteasome inhibitors and the immunomodulatory drugs used in MM. They are needed to prevent progression of the renal involvement and improve renal prognosis.

Background and Aims Survival of patients with Multiple Myeloma (MM), Light Chain Amyloidosis (LCA) and Monoclonal Gammopathies of renal significance (MGRS) on chronic renal replacement therapy (RRT) is poor. The gold standand treatment of plasma cell dyscrasias (PCD) is high-dose chemotherapy followed by Autologous Stem Cell Transplantation (ASCT) which can induce complete remission and longer survival than chemotherapy alone. Kidney transplantation (KT) after ASCT could represent an option for patients with PCD and End Stage Renal Disease (ESRD). There is no evidence about the time of follow up required from MM remission and KT. Method We present a case series of 5 patients who underwent KT after ASCT and remission of MM among 2,500 transplant recipients followed at the Nephrology Dialysis and Renal Transplantation Unit of S.Orsola University Hospital from 1967 untill now. As in case of recovery from solid cancers, the feasibility of KT after MM was considered when no signs of relapse were assessed. In our cohort 3 patients were affected by Light Chain Deposition Disease (LCDD), 1 patient presented Myeloma Cast Nephropathy (MCN) and one patient Light Chain Amyloidosis (LCA). They all required RRT and underwent KT after ASCT. Results Time between ASCT and KT ranged from 3 and 11 years and clinical outcome was very different. The mean follow up period ranged from 2 to 4 years. In the first case (LCDD) KT was performed 11 years after ASCT, the graft failure occurred 6 years later because of chronic allograft nephropathy requiring RRT. In the second case (LCDD) patient received KT 3 years after ASCT. He developed Bence-Jones proteinuria requiring specific therapy with Dexametasone and Bortezomib determining progressive graft failure. In the third case (LCDD) KT was performed 4 years after ASCT and the 4 year follow up is negative for relapse of MM or ESRD. The fourth patient presented MCN and received KT 8 years after ASCT. MCN relapsed 6 years later; it caused ESRD requiring RRT. In the last patient (LCA) KT was performed 4 years after ASCT. No recurrence occurred in a 2-year follow up. Conclusion MM is the most frequent malignancy in dialytic population; the need for KT in MM remains high. ASCT improves the quality of life and offers higher survival in patients with myeloma/MGRS/amyloidosis-related ESRD. Therefore the combination of chemotherapy/ASCT and KT is pivotal to pursue renal restoring. Since high risk of recurrence larger study are required to clarify the better follow up period after MM remission and KT.

Background and objectives FSGS recurrence after kidney transplantation is a major risk factor for graft loss. However, the natural history, clinical predictors, and response to treatment remain unclear because of small sample sizes and poor generalizability of single-center studies, and disease misclassification in registry-based studies. We therefore aimed to determine the incidence, predictors, and treatment response of recurrent FSGS in a large cohort of kidney transplant recipients. Design, setting, participants, & measurements The Post-Transplant Glomerular Disease (TANGO) project is an observational, multicenter, international cohort study that aims to investigate glomerular disease recurrence post-transplantation. Transplant recipients were screened for the diagnosis of idiopathic FSGS between 2005 and 2015 and details were recorded about the transplant, clinical outcomes, treatments, and other risk factors. Results Among 11,742 kidney transplant recipients screened for FSGS, 176 had a diagnosis of idiopathic FSGS and were included. FSGS recurred in 57 patients (32%; 95% confidence interval [95% CI], 25% to 39%) and 39% of them lost their graft over a median of 5 (interquartile range, 3.0–8.1) years. Multivariable Cox regression revealed a higher risk for recurrence with older age at native kidney disease onset (hazard ratio [HR], 1.37 per decade; 95% CI, 1.09 to 1.56). Other predictors were white race (HR, 2.14; 95% CI, 1.08 to 4.22), body mass index at transplant (HR, 0.89 per kg/m2; 95% CI, 0.83 to 0.95), and native kidney nephrectomies (HR, 2.76; 95% CI, 1.16 to 6.57). Plasmapheresis and rituximab were the most frequent treatments (81%). Partial or complete remission occurred in 57% of patients and was associated with better graft survival. Conclusions Idiopathic FSGS recurs post-transplant in one third of cases and is associated with a five-fold higher risk of graft loss. Response to treatment is associated with significantly better outcomes but is achieved in only half of the cases.

INTRODUCTION AND AIMS: CPFA (Coupled plasma filtration and adsorption) is currently used in the treatment of severe sepsis with the intention of removing the proinflammatory mediators from the systemic circulation. Some evidence exist about the bilirubin adsorbing ability of the neutral styrenic resin which is part of the extracorporeal circuit of CPFA. The aim of this study is to assess efficacy and safety of CPFA in extracorporeal detoxification of liver toxins in patients affected by acute or acute-onchronic liver failure (Figure 1). METHODS: Twelve patients (age 23 - 73 years) with acute (n ¼ 3) or acute-on-chronic (n ¼ 9) liver failure were enrolled. A total of 31 CPFA treatments were carried out. Each CPFA treatment lasted 6 hours. Unfractionated heparin was used as anticoagulation of the extracorporeal circuit in 19 CPFA sessions; citrate anticoagulation with the concomitant infusion of calcium chloride in 12 CPFA sessions. The number of treatment for each patient was established on his/her clinical status. The reduction ratios per session of bilirubin and bile acids were considered. Hemoglobin, platelets, white blood cells, coagulation tests, urea, creatinine and electrolytes were also checked on starting CPFA and at the end of CPFA, as biocompatibility measures. RESULTS: All sessions were well tolerated by the patients. Alcohol was the most common etiology of the liver injury (n ¼ 9), 1 patient was affected by acute cholangitis and Fisher-Evans syndrome, 1 had a viral etiology, and 1 patient had a postoperative jaundice. Median reduction rate per session for total bilirubin was 28.8% (range 2.2 - 40.5); for direct bilirubin was 32.7 (range 8.3 - 48.9); for indirect bilirubin was 29.5% (range 6.5 - 65.4); for bile acids was 28.9% (16.7 - 59.7); for lactic acid was 30% (range -57.2%- 55.6%). In 10 out of 12 patients was observed a recovery of liver function. At one year of follow-up 2 patients died during the hospitalization; 6 patients are followed like outpatients, recovered their basal liver function and 1 of them is no more in the waiting list for the transplant. As to the remaining 4 patients who have not yet completed the one year follow-up, 2 out of 4 are still alive after a 6-month follow-up and recovered their basal liver function, 1 patient underwent a successful liver transplantation, the last patient is still alive after a 3-month follow up. CONCLUSIONS: Although CPFA is a non-standardized technique for the liver failure, its use in patients with acute or acute-on-chronic liver failure has shown favorable effects on safety and efficacy in terms of detoxification. Thus it is considerable a “bridge technique” toward the liver transplant and the recovery of basal liver function.